Frequency of Agreement Between Structural and Functional Glaucoma Testing: A Longitudinal Study of 3D OCT and Current Clinical Tests.

PURPOSE: To evaluate how often tests of structure and function detect glaucoma progression at the same study visit. Tests include current glaucoma clinical tests and a new 3-dimensional (3D) optical coherence tomography (OCT) rim measurement. DESIGN: Prospective cohort study. METHODS: For 124 open-angle glaucoma patients at a single institution, one eye was randomly selected for each patient. Patients were included if they had open-angle glaucoma and if they had at least 4 yearly study visits. Study visits included a full dilated eye exam, disc photography (DP), Humphrey visual field (HVF 24-2) testing, 2D OCT retinal nerve fibre layer (RNFL) thickness measurements, and 3D OCT neuroretinal rim measurements (i.e., minimum distance band or MDB). For each test at each study visit, eyes were classified as progressors or non-progressors using event-based analysis. Agreement occurred if tests progressed in the same eye at the same study visit. Agreements between all compared tests were calculated as percentages of agreement. RESULTS: The study included 124 open-angle glaucoma eyes, which had an average follow-up period of 66.9 ± 16.4 months. Structural tests (i.e., DP, global RNFL thickness, and global MDB rim thickness) progressed at the same visit as the functional test (i.e., HVF testing) in only 5.0% (3/60) to 16.0% (13/81) of eyes. Global MDB thickness and global RNFL thickness showed similar agreement with functional HVF testing (i.e., 16.0% [13/81] and 8.3% [7/84], respectively), and global MDB thickness showed better structure-function agreement with HVF testing than between DP and HVF testing (i.e., 5.0% [3/60], P = 0.04). For all paired comparisons between testing methods, eyes with moderate glaucoma showed similar or better agreement than eyes with mild or severe glaucoma. CONCLUSIONS: Clinical tests of structure and function do not usually progress at the same clinic visit. Most of the time, glaucoma progression is only detected by one or two tests.

Reproducibility of Neuroretinal Rim Measurements Obtained from High-Density Spectral Domain Optical Coherence Tomography Volume Scans.

Purpose: To compare the reproducibility of two-dimensional (2D) peripapillary retinal nerve fiber layer (RNFL) thickness and three-dimensional (3D) neuroretinal rim measurements using spectral domain optical coherence tomography (SDOCT) in normal and glaucoma subjects. Methods: One eye per subject for 27 normal and 40 glaucoma subjects underwent repeat SDOCT RNFL thickness scans and optic nerve volume scans on the same day. From the volume scan, custom software calculated five neuroretinal rim parameters: 3D minimum distance band (MDB) thickness, 3D MDB area, 3D rim volume, 2D rim area, and 2D rim thickness. Within-subject variance (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC) were analyzed. Results: MDB thickness and RNFL thickness have similar reproducibility among normal and glaucoma subjects (eg, global MDB thickness CVs of 2.4% and 3.6%, and global RNFL thickness CVs of 1.3% and 2.2%; P > 0.05 for both comparisons). Reproducibility of MDB thickness was lower in glaucoma patients for the superior and inferior quadrants compared to normal subjects (CVs of 9.6% versus 3.4% and 6.9% versus 2.7%; P < 0.05, respectively). There were no statistically significant differences between both groups for RNFL thickness in the four quadrants. For both patient groups and for all regions, MDB thickness had the lowest CVs among all five neuroretinal rim parameters (eg, global MDB thickness CVs of 2.4% and 3.6% versus 3.0% and 18.9% for the other four neuroretinal rim parameters). Conclusion: Global MDB and global RNFL thickness are similarly reproducible among normal and glaucoma subjects, though MDB thickness for the superior and inferior quadrants is less reproducible among glaucoma subjects.

Disc Hemorrhages Are Associated With Localized Three-Dimensional Neuroretinal Rim Thickness Progression in Open-Angle Glaucoma.

PURPOSE: To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. DESIGN: Prospective cohort study. METHODS: A longitudinal study was undertaken of 124 open-angle glaucoma patients who had yearly disc photography, visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3-dimensional (3D) neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or glaucoma nonprogressors using event-based analysis. RESULTS: Of 124 open-angle glaucoma patients, 19 (15.3%) had 1 or more DHs on yearly disc photographs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; odds ratio: 3.96; P = .04) but not with global or inferior MDB progression (P = .14 and .81, respectively), DP progression (P = .08), VF progression (P = .45), or RNFL global, inferior, or superior progression (P = .17, .26, and .76, respectively). In the majority of patients with MDB progression (14/17 or 82%), the progression was noted before or concurrently with the first instance of DH. CONCLUSIONS: Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.

Facilitating glaucoma diagnosis with intereye neuroretinal rim asymmetry analysis using spectral-domain optical coherence tomography.

Purpose: To determine whether intereye asymmetry of a three-dimensional neuroretinal rim parameter, the minimum distance band, is useful in differentiating normal eyes from those with open-angle glaucoma. Materials and Methods: This is a cross-sectional study of 28 normal subjects and 33 glaucoma subjects. Subjects underwent spectral domain optical coherence tomography imaging of both eyes. From high-density raster scans of the optic nerve head, a custom-designed segmentation algorithm calculated mean minimum distance band neuroretinal rim thickness globally, for four quadrants, and for four sectors. Intereye minimum distance band thickness asymmetry was calculated as the absolute difference in minimum distance band thickness values between the right and left eyes. Results: Increasing global minimum distance band thickness asymmetry was not associated with increasing age or increasing refractive error asymmetry. Glaucoma patients had thinner mean neuroretinal rim thickness values compared to normal patients (209.0 µm vs 306.0 µm [P < 0.001]). Glaucoma subjects had greater intereye thickness asymmetry compared to normal subjects for the global region (51.9 µm vs 17.6 µm [P < 0.001]) as well as for all quadrants and all sectors. For detecting glaucoma, a thickness asymmetry value >28.3 µm in the inferior quadrant yielded the greatest sum of sensitivity (87.9%) and specificity (75.0%). Globally, thickness asymmetry >30.7 µm yielded the greatest sum of sensitivity (66.7%) and specificity (89.3%). Conclusions: This study indicates that intereye neuroretinal rim minimum distance band asymmetry measurements, using high-density spectral domain optical coherence tomography volume scans, may be an objective and quantitative tool for assessing patients suspected of open-angle glaucoma.

Structure-Function Mapping Using a Three-Dimensional Neuroretinal Rim Parameter Derived From Spectral Domain Optical Coherence Tomography Volume Scans.

Purpose: To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods: Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results: The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions: Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Earlier Detection of Glaucoma Progression Using High-Density 3-Dimensional Spectral-Domain OCT Optic Nerve Volume Scans.

PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. DESIGN: Prospective, longitudinal cohort study. PARTICIPANTS: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. METHODS: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test-retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 methods. RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095-0.300). CONCLUSIONS: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).

Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model.

PRECIS: In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. PURPOSE: To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. METHODS: In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. RESULTS: Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P<0.014). Below 31% of global MDB thickness, and 36.8% and 43.6% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates. CONCLUSIONS: When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.

Artifact Rates for 2D Retinal Nerve Fiber Layer Thickness Versus 3D Neuroretinal Rim Thickness Using Spectral-Domain Optical Coherence Tomography.

Purpose: To compare the rates of clinically significant artifacts for two-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness versus three-dimensional (3D) neuroretinal rim thickness using spectral-domain optical coherence tomography (SD-OCT). Methods: Only one eye per patient was used for analysis of 120 glaucoma patients and 114 normal patients. For RNFL scans and optic nerve scans, 15 artifact types were calculated per B-scan and per eye. Neuroretinal rim tissue was quantified by the minimum distance band (MDB). Global MDB neuroretinal rim thicknesses were calculated before and after manual deletion of B-scans with artifacts and subsequent automated interpolation. A clinically significant artifact was defined as one requiring manual correction or repeat scanning. Results: Among glaucomatous eyes, artifact rates per B-scan were significantly more common in RNFL scans (61.7%, 74 of 120) compared to B-scans in neuroretinal rim volume scans (20.9%, 1423 of 6820) (95% confidence interval [CI], 31.6-50.0; P < 0.0001). For clinically significant artifact rates per eye, optic nerve scans had significantly fewer artifacts (15.8% of glaucomatous eyes, 13.2% of normal eyes) compared to RNFL scans (61.7% of glaucomatous eyes, 25.4% of normal eyes) (glaucoma group: 95% CI, 34.1-57.5, P < 0.0001; normal group: 95% CI, 1.3-23.3, P = 0.03). Conclusions: Compared to the most commonly used RNFL thickness scans, optic nerve volume scans less frequently require manual correction or repeat scanning to obtain accurate measurements. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Artifact Rates for 2D Retinal Nerve Fiber Layer Thickness Versus 3D Retinal Nerve Fiber Layer Volume.

Purpose: To compare artifact rates in two-dimensional (2D) versus three-dimensional (3D) retinal nerve fiber layer (RNFL) scans using Spectralis optical coherence tomography (OCT). Methods: Thirteen artifact types in 2D and 3D RNFL scans were identified in 106 glaucomatous eyes and 95 normal eyes. Artifact rates were calculated per B-scan and per eye. In 3D volume scans, artifacts were counted only for the 97 B-scans used to calculate RNFL parameters for the 2.5-3.5-mm annulus. 3D RNFL measurements were calculated twice, once before and again after deletion of B-scans with artifacts and subsequent automated interpolation. Results: For 2D scans, artifacts were present in 58.5% of B-scans (62 of 106) in glaucomatous eyes. For 3D scans, a mean of 35.4% of B-scans (34.3 of 97 B-scans per volume scan) contained an artifact in 106 glaucomatous eyes. For 3D data of glaucoma patients, mean global RNFL thickness values were similar before and after interpolation (77.0 ± 11.6 µm vs. 75.1 ± 11.2 µm, respectively; P = 0.23). Fewer clinically significant artifacts were noted in 3D RNFL scans, where only 7.5% of glaucomatous eyes (8 of 106) and 0% of normal eyes (0 of 95) had artifacts, compared to 2D RNFL scans, where 58.5% of glaucomatous eyes (62 of 106) and 14.7% of normal eyes (14 of 95) had artifacts. Conclusions: Compared to 2D RNFL scans, 3D RNFL volume scans less often require manual correction to obtain accurate measurements. Translational Relevance: 3D RNFL volume scans have fewer clinically significant artifacts compared to 2D RNFL thickness scans.

Analysis of Neuroretinal Rim by Age, Race, and Sex Using High-Density 3-Dimensional Spectral-Domain Optical Coherence Tomography.

PRéCIS:: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. PURPOSE: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. METHODS: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch's membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. RESULTS: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P<0.001). African Americans had thinner MDBs compared with whites (P=0.003). Males and females had similar MDB thickness values (P=0.349). CONCLUSION: Neuroretinal rim MDB thickness measurements decreased significantly with age. African Americans had thinner MDB neuroretinal rims than whites.

Three-Dimensional Optical Coherence Tomography Imaging For Glaucoma Associated With Boston Keratoprosthesis Type I and II.

PRECIS: Three-dimensional (3D) spectral domain optical coherence tomography (OCT) volume scans of the optic nerve head (ONH) and the peripapillary area are useful in the management of glaucoma in patients with a type I or II Boston Keratoprosthesis (KPro). PURPOSE: The purpose of this study was to report the use of spectral domain OCT in the management of glaucoma in patients with a type I or II Boston KPro. MATERIALS AND METHODS: This study is an observational case series. Four consecutive patients with KPro implants were referred for glaucoma evaluation. A comprehensive eye examination was performed which included disc photography, visual field testing, and high-density spectral domain OCT volume scans of the ONH and the peripapillary area. 2D and 3D parameters were calculated using custom-designed segmentation algorithms developed for glaucoma management. RESULTS: Spectral domain OCT parameters provided useful information in the diagnosis and management of 4 KPro patients. OCT parameters which can be used in KPro patients included 2D retinal nerve fiber layer (RNFL) thickness, 3D peripapillary RNFL volume, 3D peripapillary retinal thickness and volume, 3D cup volume, and 3D neuroretinal rim thickness and volume. In 3 of 4 cases where the traditional 2D RNFL thickness scan was limited by artifacts, 3D spectral domain OCT volume scans provided useful quantitative objective measurements of the ONH and peripapillary region. Therefore, 3D parameters derived from high-density volume scans as well as radial scans of the ONH can be used to overcome the limitations and artifacts associated with 2D RNFL thickness scans. CONCLUSIONS: Spectral domain OCT volume scans offer the possibility to enhance the evaluation of KPro patients with glaucoma by using both 2D and 3D diagnostic parameters that are easily obtained in a clinic setting.

Diagnostic Capability of 3D Peripapillary Retinal Volume for Glaucoma Using Optical Coherence Tomography Customized Software.

PRéCIS:: The diagnostic capability of peripapillary retinal volume is similar to peripapillary retinal nerve fiber layer thickness for diagnosing glaucoma, but with fewer artifacts. PURPOSE: To compare the diagnostic capability of 3-dimensional peripapillary retinal volume (RV) versus 2-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness for open-angle glaucoma. PATIENTS AND METHODS: A retrospective cross-sectional analysis was conducted. A total of 180 subjects (113 open-angle glaucoma, 67 normal participants) had spectral domain optical coherence tomography volume scans and RNFL thickness measurements. Peripapillary RV values were calculated using a custom-designed program with 4 circumpapillary annuli (CA): CA1 had circle diameters of 2.5 and 3.5 mm; CA2, 3 and 4 mm; CA3, 3.5 and 4.5 mm; and CA4, 4 and 5 mm. Area under the receiver operating characteristic curves were calculated for global, quadrant, and octant regions for RV (CA1 to CA4) and RNFL thickness. Pair-wise comparisons were conducted. Artifacts rates were determined. RESULTS: Mean age was 62.7±15.4 years, and 47.8% (86/180) were male. Among RV measurements, best diagnostic performances were for the smallest 2 annuli for inferior RV (CA1: 0.964, CA2: 0.955). Of the 4 annuli, CA1 had the highest diagnostic performance. Of specific regions, the inferior RV quadrant had the highest performance across CA1 to CA4. Peripapillary RV had similar diagnostic capability compared with RNFL thickness (P>0.05). The artifact rate per B-scan for RV was 6.0%, which was significantly lower compared with 2-dimensional RNFL thickness in the same patient population (32.2%, P<0.0001). CONCLUSIONS: The diagnostic capability of RV is similar to RNFL thickness for perimetric open-angle glaucoma, but RV had fewer artifacts compared with RNFL thickness.

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans.

PURPOSE: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. METHODS: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. RESULTS: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. CONCLUSIONS: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. TRANSLATIONAL RELEVANCE: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters.

Diagnostic Capability of Three-Dimensional Macular Parameters for Glaucoma Using Optical Coherence Tomography Volume Scans.

Purpose: To compare the diagnostic capability of three-dimensional (3D) macular parameters against traditional two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography. To determine if manual correction and interpolation of B-scans improve the ability of 3D macular parameters to diagnose glaucoma. Methods: A total of 101 open angle glaucoma patients (29 with early glaucoma) and 57 healthy subjects had peripapillary 2D RNFL thickness and 3D macular volume scans. Four parameters were calculated for six different-sized annuli: total macular thickness (M-thickness), total macular volume (M-volume), ganglion cell complex (GCC) thickness, and GCC volume of the innermost 3 macular layers (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer). All macular parameters were calculated with and without correction and interpolation of frames with artifacts. The areas under the receiver operating characteristic curves (AUROC) were calculated for all the parameters. Results: The 3D macular parameter with the best diagnostic performance was GCC-volume-34, with an inner diameter of 3 mm and an outer of 4 mm. The AUROC for RNFL thickness and GCC-volume-34 were statistically similar for all regions (global: RNFL thickness 0.956, GCC-volume-34 0.939, P value = 0.3827), except for the temporal GCC-volume-34, which was significantly better than temporal RNFL thickness (P value = 0.0067). Correction of artifacts did not significantly change the AUROC of macular parameters (P values between 0.8452 and 1.0000). Conclusions: The diagnostic performance of best macular parameters (GCC-volume-34 and GCC-thickness-34) were similar to or better than 2D RNFL thickness. Manual correction of artifacts with data interpolation is unnecessary in the clinical setting.

Volumetric Measurement of Optic Nerve Head Drusen Using Swept-Source Optical Coherence Tomography.

PURPOSE: To describe new software tools for quantifying optic nerve head drusen volume using 3-dimensional (3D) swept-source optical coherence tomography (SS-OCT) volumetric scans. MATERIALS AND METHODS: SS-OCT was used to acquire raster volume scans of 8 eyes of 4 patients with bilateral optic nerve head drusen. The scans were manually segmented by 3 graders to identify the drusen borders, and thereafter total drusen volumes were calculated. Linear regression was performed to study the relationships between drusen volume, retinal nerve fiber layer thickness, and Humphrey visual field mean deviation. RESULTS: In the 8 study eyes, drusen volumes ranged between 0.24 to 1.05 mm. Visual field mean deviation decreased by ∼20 dB per cubic millimeter increase in drusen volume, and the coefficient of correlation of the linear regression was 0.92. In this small patient series, visual field defects were detected when drusen volume was larger than about 0.2 mm. CONCLUSIONS: Software tools have been developed to quantify the size of OHND using SS-OCT volume scans.

Diagnostic Capability of Peripapillary Three-dimensional Retinal Nerve Fiber Layer Volume for Glaucoma Using Optical Coherence Tomography Volume Scans.

PURPOSE: To determine the diagnostic capability of peripapillary 3-dimensional (3D) retinal nerve fiber layer (RNFL) volume measurements from spectral-domain optical coherence tomography (OCT) volume scans for open-angle glaucoma (OAG). DESIGN: Assessment of diagnostic accuracy. METHODS: Setting: Academic clinical setting. STUDY POPULATION: Total of 180 patients (113 OAG and 67 normal subjects). OBSERVATION PROCEDURES: One eye per subject was included. Peripapillary 3D RNFL volumes were calculated for global, quadrant, and sector regions, using 4 different-size annuli. Peripapillary 2D RNFL thickness circle scans were also obtained. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios. RESULTS: Among all 2D and 3D RNFL parameters, best diagnostic capability was associated with inferior quadrant 3D RNFL volume of the smallest annulus (AUROC value 0.977). Otherwise, global 3D RNFL volume AUROC values were comparable to global 2D RNFL thickness AUROC values for all 4 annulus sizes (P values: .0593 to .6866). When comparing the 4 annulus sizes for global RNFL volume, the smallest annulus had the best AUROC values (P values: .0317 to .0380). The smallest-size annulus may have the best diagnostic potential, partly owing to having no areas excluded for being larger than the 6 × 6 mm2 scanned region. CONCLUSION: Peripapillary 3D RNFL volume showed excellent diagnostic performance for detecting glaucoma. Peripapillary 3D RNFL volume parameters have the same or better diagnostic capability compared to peripapillary 2D RNFL thickness measurements, although differences were not statistically significant.

Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration.

PURPOSE: To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients with AMD and a comparison group (>50 years) without any vitreoretinal disease. METHODS: All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2° circle, 5° superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. MAIN OUTCOME MEASURES: The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. RESULTS: We included 137 eyes (n = 77 subjects), 72.3% (n = 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot (ß = 4.8, P < 0.001), as well as any abnormalities in the macula (ß = 2.4, P = 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n = 76, 55.5%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs (ß = 2.00, P = 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P = 0.001 for both) or anywhere in the macula (P < 0.001 for both). Within the testing spot, the presence of classic drusen or serous pigment epithelium detachment was also significantly associated with impairments in DA (P ≤ 0.018). CONCLUSIONS: Our results suggest a significant association between macular morphology evaluated by OCT and time to dark-adapt. Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly associated with impaired dark adaptation.

Automated Brightness and Contrast Adjustment of Color Fundus Photographs for the Grading of Age-Related Macular Degeneration.

PURPOSE: The purpose of this study was to develop an algorithm to automatically standardize the brightness, contrast, and color balance of digital color fundus photographs used to grade AMD and to validate this algorithm by determining the effects of the standardization on image quality and disease grading. METHODS: Seven-field color photographs of patients (>50 years) with any stage of AMD and a control group were acquired at two study sites, with either the Topcon TRC-50DX or Zeiss FF-450 Plus cameras. Field 2 photographs were analyzed. Pixel brightness values in the red, green, and blue (RGB) color channels were adjusted in custom-built software to make the mean brightness and contrast of the images equal to optimal values determined by the Age-Related Eye Disease Study (AREDS) 2 group. RESULTS: Color photographs of 370 eyes were analyzed. We found a wide range of brightness and contrast values in the images at baseline, even for those taken with the same camera. After processing, image brightness variability (brightest image-dimmest image in a color channel) was reduced 69-fold, 62-fold, and 96-fold for the RGB channels. Contrast variability was reduced 6-fold, 8-fold, and 13-fold, respectively, after adjustment. Of the 23% images considered nongradable before adjustment, only 5.7% remained nongradable. CONCLUSIONS: This automated software enables rapid and accurate standardization of color photographs for AMD grading. TRANSLATIONAL RELEVANCE: This work offers the potential to be the future of assessing and grading AMD from photos for clinical research and teleimaging.

Enhanced Diagnostic Capability for Glaucoma of 3-Dimensional Versus 2-Dimensional Neuroretinal Rim Parameters Using Spectral Domain Optical Coherence Tomography.

PURPOSE: To compare the diagnostic capability of 3-dimensional (3D) neuroretinal rim parameters with existing 2-dimensional (2D) neuroretinal and retinal nerve fiber layer (RNFL) thickness rim parameters using spectral domain optical coherence tomography (SD-OCT) volume scans. MATERIALS AND METHODS: Design: Institutional prospective pilot study. STUDY POPULATION: 65 subjects (35 open-angle glaucoma patients, 30 normal patients). OBSERVATION PROCEDURES: One eye of each subject was included. SD-OCT was used to obtain 2D RNFL thickness values and 5 neuroretinal rim parameters [ie, 3D minimum distance band (MDB) thickness, 3D Bruch's membrane opening-minimum rim width (BMO-MRW), 3D rim volume, 2D rim area, and 2D rim thickness]. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve values, sensitivity, and specificity. RESULTS: Comparing all 3D with all 2D parameters, 3D rim parameters (MDB, BMO-MRW, rim volume) generally had higher area under the receiver operating characteristic curve values (range, 0.770 to 0.946) compared with 2D parameters (RNFL thickness, rim area, rim thickness; range, 0.678 to 0.911). For global region analyses, all 3D rim parameters (BMO-MRW, rim volume, MDB) were equal to or better than 2D parameters (RNFL thickness, rim area, rim thickness; P-values from 0.023 to 1.0). Among the three 3D rim parameters (MDB, BMO-MRW, and rim volume), there were no significant differences in diagnostic capability (false discovery rate >0.05 at 95% specificity). CONCLUSIONS: 3D neuroretinal rim parameters (MDB, BMO-MRW, and rim volume) demonstrated better diagnostic capability for primary and secondary open-angle glaucomas compared with 2D neuroretinal parameters (rim area, rim thickness). Compared with 2D RNFL thickness, 3D neuroretinal rim parameters have the same or better diagnostic capability.

Diagnostic Capability of Peripapillary Retinal Volume Measurements in Glaucoma.

PURPOSE: To determine the diagnostic capability of spectral domain optical coherence tomography peripapillary retinal volume (RV) measurements. MATERIALS AND METHODS: A total of 156 patients, 89 primary open-angle glaucoma and 67 normal subjects, were recruited. Spectral domain optical coherence tomography peripapillary RV was calculated for 4 quadrants using 3 annuli of varying scan circle diameters: outer circumpapillary annuli of circular grids 1, 2, and 3 (OCA1, OCA2, OCA3). Area under the receiver operating characteristic curves and pairwise comparisons of receiver operating characteristic (ROC) curves were performed to determine which quadrants were best for diagnosing primary open-angle glaucoma. The pairwise comparisons of the best ROC curves for RV and retinal nerve fiber layer (RNFL) were performed. The artifact rates were analyzed. RESULTS: Pairwise comparisons showed that the smaller annuli OCA1 and OCA2 had better diagnostic performance than the largest annulus OCA3 (P<0.05 for all quadrants). OCA1 and OCA2 had similar diagnostic performance, except for the inferior quadrant which was better for OCA1 (P=0.0033). The pairwise comparisons of the best ROC curves for RV and RNFL were not statistically significant. RV measurements had lower rates of artifacts at 7.4% while RNFL measurements had higher rates at 42.9%. CONCLUSIONS: Peripapillary RV measurements have excellent ability for diagnosing not only glaucoma patients but also a subset of early glaucoma patients. The inferior quadrant of peripapillary annulus OCA1 demonstrated the best diagnostic capability for both glaucoma and early glaucoma. The diagnostic ability of RV is comparable with that of RNFL parameters in glaucoma but with lower artifact rates.